Efficient Synthesis of Primary Selenocarboxylic Amides by Reaction of Nitriles with Phosphorous(V) Selenide

Abstract

The reaction of nitriles with P₂Se₅ in the presence of EtOH/H₂O afforded a variety of primary selenocarboxylic amides.

Key words

cyclizations - heterocycles - nitriles - selenium - synthetic methodology

References

• 1 Goldstein BM. Kennedy SD. Hennen WJ. J. Am. Chem. Soc.  1990,  112:  8265 ; and references cited therein
• 2a Larsen R. In Comprehensive Heterocyclic Chemistry II   Vol. 3:  Shinkai I. Elsevier Science; Oxford: 1996.  Chap. 8.
• 2b Wirth T. Organoselenium Chemistry, Modern Developments in Organic Synthesis   Springer; Berlin: 2000. 
• 2c Koketsu M. Nada F. Ishihara H. Synthesis  2002,  195 ; and references cited therein
• 3a Lai L.-L. Reid DH. Synthesis  1993,  870 
• 3b Klayman DL. Griffins TS. J. Am. Chem. Soc.  1973,  95:  197 
• 3c For the use of LiAlH₄/Se, see: Ishihara H. Koketsu M. Fukuta Y. Nada F. J. Am. Chem. Soc.  2001,  123:  8408 
• 3d Also see: Koketsu M. Fukuta Y. Ishihara H. Tetrahedron Lett.  2001,  42:  6333 
• 4 Ogawa A. Miyaka J. Karasaki Y. Murai S. Sonoda N. J. Org. Chem.  1985,  50:  384 
• 5 Kaminski R. Glass RS. Skowronska A. Synthesis  2001,  1308 
• 6 Cohen VJ. Synthesis  1978,  668 
• This can have several reasons:
• 7a We have found that the aluminothermic formation of Al₂Se₃ from the elements is often not complete and strongly depends on the particle size of aluminum and on many other parameters: Brauer B. Handbuch der präparativen anorganischen Chemie   Ferd. Enke Verlag; Stuttgart: 1960.  p.732 
• 7b

  It is necessary, but extremely difficult to remove remaining aluminum. In addition, Al₂Se₃ is very prone to hydrolysis and has to be handled with great care (glove box). Since it has to be used as a powder, substantial decomposition readily occurs and impurities cannot be separated.

• 8 For the synthesis of thioamides from amides, see: Raucher S. Klein P. J. Org. Chem.  1981,  46:  3558 
• For the synthesis of N,N-disubstituted selenocarboxylic amides, see:
• 9a Collhard-Charon C. Renson M. Bull. Soc. Chim. Belg.  1963,  72:  304 
• 9b Jensen KA. Nielsen PH. Acta Chim. Scand.  1966,  20:  597 
• 9c See also: Sukhai RS. de Jong R. Brandsma L. Synthesis  1977,  888 
• 10 General procedure for the preparation of selenocarboxylic amides: Method A (for 2a-2t): An ethanol solution (15-30 mL) of the nitrile (50 mmol) and of freshly prepared P₂Se₅ (9.1 g, 20 mmol) was refluxed. Subsequently, water (3-6 mL) was added dropwise during 2-3 h. After cooling, the solution was filtered and water was added to the filtrate which resulted in precipitation of the selenocarboxylic amide 2. In some cases, the aqueous layer was extracted with ether or benzene. The combined organic layers were dried (Na₂SO₄), filtered and concentrated. Cooling (dry ice) or addition of petroleum ether resulted in crystallization of the product. The crude product was dried (desiccator, P₂O₅) and crystallized from the solvent indicated (Table 2).Method B (for 2u-2y): The nitrile (50 mmol) was dissolved in ethanol (15-30 mL) and water (3-6 mL). To the refluxing solution was added freshly prepared P₂Se₅ (9.1 g, 20 mmol) in small portions during 2-3 h. The solution was cooled and filtered. Water was added to the filtrate which resulted in precipitation of the selenocarboxylic amide 2. In some cases, the aqueous layer was extracted with benzene. The combined organic layers were dried (Na₂SO₄), filtered and concentrated. Cooling (dry ice) or addition of petroleum ether resulted in crystallization of the product. The crude product was dried (exsiccator, P₂O₅) and crystallized from the solvent indicated (Table 2). For 2x, only water was used as the solvent. In case of 2x and 2y, the hot solution was filtered without prior cooling. Concentration of the filtrate resulted in precipitation of the pure product.Spectroscopic data of 2-methyl-selenobenzamide (2b): ¹H NMR (C₆D₆, 300 MHz): δ 2.15 (s, 3 H, CH₃), 5.90 (br, 1 H, NH), 6.78-7.22 (m, 4 H, Ar), 8.20 (br, 1 H, NH). ¹³C NMR (C₆D₆, 75 MHz): δ_c 19.67 (CH₃), 125.67, 125.68, 126.22, 126.24, 128.99, 130.70 (Ar), 210.46 (C=Se). IR (KBr, cm^-1): 1620 (s), 1420 (s), 1290 (m), 1265 (w), 1230 (w), 1155 (w), 1130 (w), 1045 (w), 855 (m). MS (70 eV): m/z (%): 199 (100, M⁺). Anal. calcd. for C₈H₉NSe (198.13): C 48.50, H 4.58, N 7.07, Se 38.86; found C 48.50, H 4.30, N 7.10, Se 39.50. All new compounds gave satisfactory analytical or high resolution mass data.Synthesis of P₂Se₅: A mixture of red phosphorous and grey selenium powder was heated in a tube with minor Bunsen burner flame until the reaction was complete. The reaction mixture was grounded and powdered to give P₂Se₅ as a grey solid. For comparison, see: Kudchadker MV. Zingaro RA. Irgolic KJ. Can. J. Chem.  1968,  46:  1415 

11

Typical procedure for the preparation of 1,3-selenazoles: An EtOH solution (20 mL) of selenobenzamide (1.84 g, 10 mmol) and α-bromoacetophenone (1.99 g, 10 mmol) was stirred under evolution of heat. After cooling, the mixture was poured into H₂O. The precipitated product was filtered off and recrystallized from EtOH to give 3a as colorless lamella (2.47 g, 87%).
Spectroscopic data of 2,4-diphenyl-1,3-selenazole (3a): mp: 99 °C. ¹H NMR (CDCl₃, 300 MHz): δ 7.38-8.01 (m, 10 H, Ar), 8.06 (s, 1 H, 5-H). ² J (SeH) = 58.3 Hz. ¹³C NMR (CDCl₃, 75 MHz): δ_c 118.26, 126.72, 127.08, 127.91, 128.70, 128.97, 130.21, 135.42, 136.41, 156.93, 173.87. ⁷⁷Se NMR (CDCl₃, 100% Me₂Se): δ 712.69 (² J _Se-H = 58.3 Hz). IR (KBr, cm^-1): 3114 (m), 1598 (s), 1509 (s), 1481 (s), 1442 (s), 1279 (m), 1152 (m), 1071 (m), 1043 (s), 1027 (m), 952 (s). MS (70 eV): m/z (%): 285 (59, M⁺), 182 (100), 102 (86). Anal. calcd. for C₁₅H₁₁NSe (284.22): C 63.39, H 3.90, N 4.93; found C 63.45, H 3.92, N 4.91. All new compounds gave satisfactory analytical or high resolution mass data.